Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare tumor and is now included in the World Health Organization tumor classification. Its prognosis is generally very poor even when the diagnosis is made at an early stage. We report a case of pure large cell neuroendocrine tumour of ovary, appearing 9 months following laparoscopic type I hysterectomy, bilateral pelvic lymph node dissection with ovarian preservation of anatomically normal looking ovaries performed for a cervical biopsy diagnosis of cervical intraepithelial neoplasia grade III with foci of invasion. The rarity lies in the rapid onset (9 months) of a large tumor following conservation of an anatomically normal ovaries. Surgical debulking and five cycles of chemotherapy (Etoposide and Cisplatin) were administered to the woman. She is on followup with no clinical or radiological evidence of disease recurrence for 6 months.
Ovarian pure large cell neuroendocrine (LCNEC) carcinoma is a rare tumour. Only 6 cases have been reported and all of them have been unilateral tumors. We report 7th case of pure LCNEC which was bilateral. They are rapid growing tumours with generally poor prognosis. Literature is replete with different modalities of adjuvant therapy. We have discussed the clinical presentation, histopathology, surgical debulking, and chemotherapy options and have also reviewed the literature.
A 40-year-old perimenopausal lady presented to us with a histopathological diagnosis of cervical intraepithelial neoplasia grade III with foci of invasion. A laparoscopic type I hysterectomy and bilateral pelvic lymphadenectomy along with conservation of normal looking ovaries was performed. She was clinically and radiologically free of disease on followup for 6 months. In the ninth month she presented with history of acute distension and pain abdomen, loss of weight and appetite, fever with chills, and itching all over the body. Her general condition was good. On abdominal examination a firm, irregular mass was felt occupying the suprapubic region and extending towards left iliac fossa, and left lumbar region, measuring
Complete haemogram, biochemistry, and chest X-ray were within normal limits. Ca-125 value was 280.80 IU/ml(high) and CEA was 7.66 ng/mL(high). Ultrasonography of abdomen and pelvis showed normal liver, gall bladder, and spleen except for left kidney with evidence of grade I hydroureteronephrosis secondary to compression by the mass. Uterus was not seen-post operative status. A large lobulated heterogenous mass lesion with few areas of necrosis in it, situated posterior to and indenting the base of the urinary bladder, measuring
During surgery minimal haemorrhagic ascites was seen in the peritoneal cavity. Bilateral solid ovarian tumours with breech and deposits on the capsule were seen. The right ovarian tumour measuring
Rt.Ov—right ovarain tumour, Lt.Ov—left ovarian tumour adherent to bladder, lateral pelvic wall, rectum and vault and burrowing into the pouch of douglas. H: haemmorhagic ascites.
Right ovarian tumour measuring
Bilateral ovaries show poorly differentiated malignant tumour-carcinoma, with wide areas of necrosis. Mitotic rate 15–20/high power field, capsular breech noted in the left ovary. Omentum showed tumour deposits, and 3 paraaortic nodes were reactive. Bowel and bladder deposits showed tumour cells, Figure
Neuroendocrine carcinoma shows clusters (C) of medium to large cells with moderate amount of cytoplasm and round to oval nuclei with even chromatin and occasionally prominent nucleoli (10x).
CK, EMA were positive. CK 7, CK 20, Inhibin and Chromogranin were negative. Focal areas were positive for Synaptophysin, suggesting a final diagnosis of Large Cell neuroendocrine Carcinoma Ovary Figure
Cluster of neuroendocrine cells showing synaptophysin positivity(S) (40x).
Postoperative adjuvant chemotherapy consisting of Etoposide 100 mg/M2 from day 1 to day 5,and Cisplatin 100 mg/M2 in divided doses on day 1 and day 2 was administered 3rd weekly for 5 cycles. Patient tolerated chemotherapy, except for in-patient admission for neutropenic fever on day 7 during the 3rd and the 4th cycle. She was given symptomatic and supportive treatment. She is on followup for 6 months and has no clinical or ultrasonographic evidence of disease recurrence.
The incidence of pure large cell neuroendocrine carcinoma (LCNEC) of ovary is very rare. Primary ovarian LCNEC is synonymous with undifferentiated carcinoma of non-small cell neuroendocrine type, according to the World Health Organization classification [
To date, only 40 cases of large cell neuroendocrine carcinoma (LCNEC) of the ovary are reported. 34 cases were associated with other histologic subtypes and 6 cases were purely LCNEC. They are generally associated with poor patient outcomes. The present case is the seventh case of pure form of ovarian large cell neuroendocrine carcinoma and the other rarity is, it is the first case arising bilaterally. This extremely rare clinical presentation of a huge mass arising from an anatomically normal ovary confirmed laparoscopically, 9 months back was reiterating the fact that this tumour was rapidly growing. Some authors have similar opinion [
The age of patients was ranging between 27–81 years and a median age of 61 years. The commonest presentation was abdominal pain and distension in 50% (3/6) of cases, similarly the present case presented with abdominal distension. The size of the tumour ranged from 9 cms to 35 cms with an average of 16 cms. The tumor was bilateral in only the present case. Left side was more common in 50% of the cases (3/6). A range of therapeutic options have been used like surgery with chemotherapy, Table
Clinicopathologic, treatment modality, and followup of women with pure large cell neuroendocrine tumour of ovary.
S. no. | Authors | Age/present. | Associated component | Site/laterality | Stage | Treatment modality | Followup |
---|---|---|---|---|---|---|---|
(1) | Behnam et al. [ |
27/pelvic mass | None | 11 cm, left | Ic | LSO/omentectomy/ |
NED 10 m |
(2) | Lindboe [ |
64/abdominal discomport | None | 14 cm, right | Ia | TAH/BSO/omentectomy/ |
NED 9 m |
(3) |
Dundr et al. [ |
73/NA | None | 9 cm, left | N/A | N/A | N/A |
(4) | Aslam et al. |
76/abdominal pain | None | 35, left |
N/A | TAH/BSO/OMT | Died soon |
(5) | Tsuji et al. [ |
46/abdominal distension | None (focal squamous differentiation) | 12, right | N/A | TAH/BSO/OMT | Died in 4 m |
(6) | Japan Oshita et al. (4 cases) [ |
42–81/N/A | Mixed epithelial carcinoma-3 cases, |
N/A | Ic |
N/A, chemotherapy—paclitaxel and carboplatin | Died in 2 m |
(7) | Present case | 40/abdominal dist., fever, itching | none | Bilateral ovarian |
IIIc | BSO/TD/TO/ /PALND/ |
NED-6 m |
AWD: alive with disease; TAH: total hysterectomy, RSO: right salpingo-oophorectomy; BSO: bilateral salpingo-oophorectomy; LSO: left salpingo-oophorectomy; N/A: no information available; NED: no evidence of disease; NOS: not otherwise specified; DOD: dead of disease; m: months; y: years.
As reported by Kim et al. [
Various combinations of chemotherapy were used, including cisplatin and cyclophosphamide followed by etoposide and cisplatin; or paclitaxel and carboplatin protocols Table
Three of the six patients have died of the disease immediately following surgery to 4 months after surgery. Present patient is on followup for last 6 months.
Out of the 6 cases of pure LCNEC, 2 cases had early stage disease and survived for a minimum of 10 months. In 3 cases there is no stage of disease mentioned but have had short survival of 4 months. One case had stage 4 disease and died after 2 months. Present case is a stage III disease who has survived for 6 months without evidence of recurrence, probably the longest Table
Due to paucity of literature and heterogeneity in presentation and response to surgery, chemotherapy, and radiation it is oblivious to predict the efficacy of surgical debulking, chemotherapy and radiation protocols, hence there is a need for prospective clinical studies for most optimal modalities of treatment. May be a combination of optimal debulking, adjuvant chemotherapy (ifosamide, mesna, and cisplatin) with close followup of patients and use of radiation when appropriate may improve the progression free and survival rates of this rare tumour.
The authors would like to thank the patient and her daughters who shared all their efforts with them. They acknowledge Dr. Pallavi, Dr. Praveen. S. Rathod, Dr. Ravi, Dr. Rajshekar, Dr. Abhilasha, and Dr. Anbukanni S. Nursing staff of A. K. ward Mrs. Padma and her team operation theatre ICU staffs—Mrs. Rukmini and her team for their valuable inputs in patient care.